The nucleus accumbens is a focal point for integration of afferent information from the ventral tegmental area (VTA), amygdala, and hippocampus. This integration is accomplished through synaptic interactions of neurons containing a variety of neurotransmitters. The goal of the proposed research is to provide an ultrastructural basis for synaptic interactions between dopaminergic neurons of the ventral tegmental-accumbens pathways and other intrinsic neurons or afferents containing Gamma-aminobutyric acid (GABA) or one or more of the many neuropeptides identified in the VTA and n. accumbens. The dopaminergic neurons will be demonstrated by the immunocytochemical localization of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and the GABA-ergic neurons by the localization of glutamic acid decarboxylase (GAD). Antisera to these two enzymes and to neurotensin and neuropeptide Y will be localized by the peroxidase-antiperoxidase (PAP) technique and by the immunogold silver method to allow the simultaneous visualization of two antigens within single sections. The pathways containing the respective enzymatic or peptidergic markers will be examined by combining immunocytochemical labeling with anterograde or retrograde transport and with anterograde degeneration. The specific questions include: (a) What is the ultrastructural morphology of the dopaminergic neurons in the n. accumbens and VTA? (b) What are the synaptic associations between dopaminergic and GABA-ergic neurons? (c) What are the synaptic associations between the dopaminergic terminals and other afferents to the n. accumbens from the hippocampus and amygdala? and (d) What are the synaptic associations between the dopaminergic neurons and neurons containing neurotensin and neuropeptide Y? The results from these studies will extend our knowledge of neurotransmitter specific interactions of the dopaminergic neurons of the mesolimbic pathway. In addition, the findings may suggest imbalances of specific neurotransmitters which underlie neuropsychiatric disorders associated with the dopaminergic neurons.